Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJ x C3H/HeJ intercrosses
Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJ x C3H/HeJ intercrosses
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DOI：
10.1007/s00335-007-9033-5
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发表时间：
2007-08-01
期刊：
影响因子：
2.5
通讯作者：
Sugiyama, Fumihiro
中科院分区：
文献类型：
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作者：
Nishihara, Eri;Tsaih, Shirng-Wern;Sugiyama, Fumihiro
在先前对15个近交系小鼠品系的研究中，我们分别在NZO/HILtJ小鼠（代谢综合征）和C3 H/HeJ小鼠（普通瘦型品系）中发现了最高和最低的收缩压。为了确定代谢综合征高血压的基因座，我们进行了数量性状基因座（QTL）分析的血压与交叉方向作为协变量分离的F-2雄性来自NZO/HILtJ和C3 H/HeJ小鼠。我们检测到三个提示性的主效应QTL影响收缩压和舒张压（SBP和DBP）。我们分析了由SBP和DBP产生的第一主成分（PC 1）来研究血压。除了SBP和DBP的所有提示性QTL（Chr 1，3和8）外，在主扫描中在PC 1中发现了Chr 4上的一个提示性QTL。同时搜索发现了两个显着的上位性位点对（Chrs 1和4，Chrs 4和8）的PC 1。多元回归分析显示，血压QTL有3个（Bpq 10，Chr 1为100 cM，Bpq 11，Chr 4为6 cM，Bpq 12，Chr 8为29 cM），可解释血压变异的29.4%。这些上位性互作QTL以Chr 4为中心构建了一个小网络，提示遗传互作在高血压发病中的重要性。在多项研究中，使用常见的近交非肥胖小鼠品系重复检测了Chrs 1，4和8上的血压QTL，这意味着大量的QTL独立于肥胖和胰岛素抵抗的发展。这些结果加深了我们对代谢性疾病中高血压复杂遗传因素的理解。
In a previous study in 15 inbred mouse strains, we found highest and lowest systolic blood pressures in NZO/HILtJ mice (metabolic syndrome) and C3H/HeJ mice (common lean strain), respectively. To identify the loci involved in hypertension in metabolic syndrome, we performed quantitative trait locus (QTL) analysis for blood pressure with direction of cross as a covariate in segregating F-2 males derived from NZO/HILtJ and C3H/HeJ mice. We detected three suggestive main-effect QTLs affecting systolic and diastolic blood pressures (SBP and DBP). We analyzed the first principle component (PC1) generated from SBP and DBP to investigate blood pressure. In addition to all the suggestive QTLs (Chrs 1, 3, and 8) in SBP and DBP, one suggestive QTL on Chr 4 was found in PC1 in the main scan. Simultaneous search identified two significant epistatic locus pairs (Chrs 1 and 4, Chrs 4 and 8) for PC1. Multiple regression analysis revealed three blood pressure QTLs (Bpq10, 100 cM on Chr 1; Bpq11, 6 cM on Chr 4; Bpq12, 29 cM on Chr 8) accounting for 29.4% of blood pressure variance. These were epistatic interaction QTLs constructing a small network centered on Chr 4, suggesting the importance of genetic interaction for development of hypertension. The blood pressure QTLs on Chrs 1, 4, and 8 were detected repeatedly in multiple studies using common inbred nonobese mouse strains, implying substantial QTL independent of development of obesity and insulin resistance. These results enhance our understanding of complicated genetic factors of hypertension in metabolic diseases.